Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat cortex.
There is an increasing body of evidence suggesting that GABA plays an important role in the therapeutic effects of antidepressant/antipanic drugs. Phenelzine and imipramine are efficacious in the treatment of depression and panic disorder and phenelzine has been reported to elevate GABA levels while imipramine enhances GABA release in rat brains. In the present study, using a multiprobe quantitative solution hybridization assay, we measured the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase (GABA-T) in rat cortex after treatment with constant infusion (via osmotic minipumps) of phenelzine or imipramine for a short-term (3 days) or long-term (21 days) period. We found that none of the treatments gave rise to significant changes in the steady-state levels of mRNAs encoding GAD67, GAD65 or GABA-T at any time point. The steady-state levels of GAT-1 mRNA were increased significantly (23%) after long-term, but not by short-term, treatment with phenelzine. Imipramine treatment, short- or long-term, did not alter the steady-state levels of GAT-1 mRNA. These results suggest that the GABA enhancing effects of phenelzine or imipramine in rat cortex do not affect the steady-state levels of mRNAs that encode GAD67, GAD65 and GABA-T. Further, the previously observed increases in GABA levels or GABA release induced by these drugs are probably not a consequence of changes in the expression of these genes.
Lai
C T
CT
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Tanay
V A
VA
Charrois
G J
GJ
Baker
G B
GB
Bateson
A N
AN
D000612:4-Aminobutyrate Transaminase / Q000235:genetics*; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D018682:GABA Agents / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D005968:Glutamate Decarboxylase / Q000235:genetics*; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D027361:Organic Anion Transporters; D010624:Phenelzine / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D018682:GABA Agents; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C493415:Slc6a1 protein, rat; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D010624:Phenelzine; D007099:Imipramine